Abstract
APOBEC3 proteins are cellular antiviral proteins that are targeted for proteasomal degradation by primate lentiviral Vif proteins. Vif acts as a substrate receptor for the Cullin5 (Cul5) E3 ubiquitin ligase, specifically interacting with Cul5 through a novel H-x5-C-x17-18-C- x3-5-H zinc binding motif. Using the membrane-permeable zinc chelator, N,N,N′,N′-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), we demonstrated a requirement for zinc for Vif function in vivo. Treatment with TPEN at an IC50 of 1.79 μM inhibits Cul5 recruitment and APOBEC3G (A3G) degradation. Zinc chelation prevented Vif function in infectivity assays, allowing the virus to become sensitive to the antiviral activity of A3G. Zinc chelation had no effect on cellular Cul5-SOCS3 E3 ligase assembly, suggesting that zinc-dependent E3 ligase assembly may be unique to HIV-1 Vif, representing a new target for novel drug design.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 217-222 |
| Number of pages | 6 |
| Journal | FASEB Journal |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
| Externally published | Yes |
Keywords
- HIV-1 virion
- Lentiviral Vif proteins
- TPEN
- Zinc binding motif
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics